System for housing/processing carrier and method for housing/processing carrier

ABSTRACT

An object is to provide a carrier housing/processing apparatus and a method wherein complicated reaction processes are simplified, and the processes can be easily performed with a small scale apparatus structure. The construction comprises; one or a plurality of carriers fixed or able to be fixed with chemical substances such as ligands; a carrier housing section which is provided with a fluid inlet/outlet and which accommodates the carrier; a drawing/discharging section which draws and discharge a fluid through the inlet/outlet with respect to the carrier housing section; and a transferring section which transfers the inlet/outlet relatively with respect to containers provided outside. Moreover, the carrier is formed in a size or a shape not allowing the carrier to pass through the inlet/outlet, and in a state of holding the carrier in the housing section, by self-weight of the carrier, frictional force between the carrier and the inner wall of the housing section, or remote force from outside with respect to the carrier, a fluid is drawn and discharged.

CROSS REFERENCE

This application is a United States national phase application ofco-pending international patent application number PCT/JP03/00316, filedJan. 16, 2003, which claims priority to Japanese patent applicationnumber 2002-9218, filed Jan. 17, 2002 which priority is claimed.

TECHNICAL FIELD

The present invention relates to a carrier housing/processing apparatusand its method. The present invention relates to all manner of fieldswhich require the handling of biological high/low molecular weightcompounds such as genes, immune systems, amino acids, proteins andsugars; including for example the fields of engineering, agriculturalscience incorporating foodstuffs, agricultural production and seafoodprocessing, pharmaceuticals, medical fields incorporating hygiene,health, immunity, disease and genetics, and scientific fields such aschemistry and biology.

In particular, the present invention is an effective method in the casewhere a series of processes using a large number of reagents andsubstances are continuously executed in a predetermined order.

BACKGROUND ART

Conventionally, in the case where a series of reaction processes using alarge number of reagents and substances are executed on a targetsubstance being a subject for examination, for example, the targetsubstance is bonded to microcarriers such as beads and accommodated in atest tube. Then, various reagents are poured into the test tube and thecarriers are separated in some way. The carriers are further transferredinto another container and other reagents are poured in, or they aresubjected to heat treatment. For example in the case where the carrieris a magnetic substance, the separation is performed by attaching ontothe inner wall of the test tube by means to a magnetic field.

Moreover, regarding a process in which the target substance is examinedusing a planar carrier such as a prepared slide fixed with, for example,various oligonucleotides, by performing a series of processes such astransferring the carrier itself into a suspension having the labeledtarget substance suspended therein, pipetting various reagents into thecarrier itself, transferring the carrier itself into a washing solution,and transferring the carrier to the measuring position of the measuringequipment so as to measure the luminescence, the base sequence structureof the target substance is examined.

In order to perform these processes, there is a problem in that thecarrier itself must be separated and transferred, causing concern ofcomplicated and time-consuming processes. In particular, in the casewhere these carriers themselves are transferred by hand, there isconcern in that the user is over burdened and cross-contamination may becaused. Moreover, when the carriers themselves are transferred bymachines, a large scaled device is needed. Furthermore, in the casewhere a non magnetic carrier is separated, it is necessary to performthe separation depending on the size and the density of the carrier,causing a problem of complicated and time-consuming processes.

On the other hand, there is a method for performing the reactionprocesses, not using a test tube nor a planar carrier, but using pipettedevice having; a pipette tip provided with a liquid passage enabling aliquid to pass therethrough, a nozzle attached with the pipette tip, amagnetic force device which exerts a magnetic field on the liquidpassage of the pipette tip, and a drawing/discharging mechanism whichdraws a fluid into the pipette tip and discharges the fluid. Accordingto this method, by drawing up a suspension suspending a large number ofmagnetic particles holding various substances on the surface, andexerting a magnetic field at the time of drawing, the magnetic particlescan be effectively attached onto the liquid passage of the pipette tipso as to perform the separation.

When using this device, since the magnetic particles can pass throughthe liquid passage, it is necessary to apply the magnetic field toattach the magnetic particles onto the inner wall so as to hold themagnetic particles in the pipette tip. Therefore, in order to performthe processes, it is necessary to complicatedly combine thedrawing/discharging control, the attraction control by the magneticfield, and the transfer control of the pipette tip. Moreover in the casewhere the carrier is a non magnetic carrier, there is a problem in thatthe separation can not be performed by the apparatus.

Therefore, it is a first object of the present invention to provide acarrier housing/processing apparatus and a method wherein, regarding acarrier which is fixed or able to be fixed with various substances, byenabling processes to be performed while accommodating and holding inthe carrier housing section, the attraction control for accommodatingand holding the carrier in the housing section and the drawing control,are made unnecessary, so that the complicated reaction processes aresimplified, and the processes can be easily performed with a small scaleapparatus structure.

It is a second object to provide a carrier housing/processing apparatusand a method wherein, regarding a carrier which is fixed or able to befixed with various substances, by accommodating and removing thesesubstances by a route which is different from a route fordrawing/discharging a fluid or substances suspended in the fluid, theprocess for separating the fluid and the carrier become unnecessary, sothat the complicated reaction processes are simplified, and theprocesses can be easily performed with a small scale apparatusstructure.

It is a third object to provide a carrier housing/processing apparatusand a method wherein, regarding a carrier which is fixed or enable to befixed with various substances, by enabling easy removal of thesubstances from the carrier housing section accommodating them, itbecomes possible to easily exchange and preserve the carrier or performother processes with respect to the carrier so that the efficiency, thereliability and the certainty of processes can be increased.

It is a fourth object to provide a carrier housing/processing apparatusand a method wherein, by appropriately determining the shape and thesize of carrier so as to not limit the material of the magneticsubstance, regardless of the material of the carrier, it becomespossible to easily separate, so that the selection range for thematerials can be increased, and the most suitable material for a processcan be selected.

DISCLOSURE OF THE INVENTION

In order to address the above technical problems, a first aspect of theinvention is a carrier housing/processing apparatus comprising; one or aplurality of carriers fixed or able to be fixed with chemical substancessuch as ligands; a carrier housing section which is provided with afluid inlet/outlet and which accommodates the carrier; adrawing/discharging section which draws and discharge a fluid throughthe inlet/outlet with respect to the carrier housing section; and atransferring section which transfers the inlet/outlet relatively withrespect to containers provided outside, wherein the carrier is formed ina size or a shape not allowing the carrier to pass through theinlet/outlet, and in a state of holding the carrier in the housingsection, by self-weight of the carrier, frictional force between thecarrier and the inner wall of the housing section, or remote force fromoutside with respect to the carrier, a fluid is drawn and discharged.

Here, “ligand” includes chemical substances including living bodies ofbiological high/low molecular weight compounds, such as for example,genetic substances such as nucleic add, proteins, sugars, sugar chains,peptides, and the like. The ligand is used as a detection substancewhich detects the bond of a receptor having bondability with the ligandto capture, separate, and extract. Receptor includes chemical substancesof biological high/low molecular weight compounds, such as; geneticsubstances such as nucleic acid, proteins, sugar chains, peptides, andthe like, having bondability with each of the genetic substances such asnucleic acid, proteins, sugar chains, peptides, and the like. ‘Fixing’includes the cases of, for example, physical attachment, electricalinteraction, and the like, as well as the cases of covalent bond andchemical absorption.

The carrier is a member which is fixed or able to be fixed with chemicalsubstances such as one or more kinds of ligands, and held by“self-weight of the carrier, frictional force with the inner wall of thehousing section, or remote force from outside with respect to thecarrier” in the carrier housing section. As a result, the holding statecan be easily released by lifting the carrier by a greater force thanthe self-weight of the carrier, moving by a force against the frictionalforce, or removing the remote force.

In this case, by providing an opening having a size enabling the carrierto pass through the carrier housing section but the opening not allowingthe fluid to pass through, it becomes possible to exchange, remove, andpreserve only the carrier in the carrier housing section. The carriermay be in the state of being bonded with predetermined ligands orreceptors in some cases, or in the state of being bonded with nosubstance in other cases. The carrier removed, preserved, and exchangedfrom the carrier housing section may further be an object of a processin other processes. Consequently, various processes become possibleenabling diversification of the processes.

In the case where the magnetic field is used as the remote force forexample, as a prerequisite, it is necessary that the carrier itself is amagnetic substance or includes a magnetic substance, and outside of thecarrier housing section there is a magnetic force device which exerts amagnetic field on the carrier housing section interior. In the casewhere an electric field is used, it is necessary that the carrier is acharged object carrying an electric charge. Moreover, the carrier isfixed with the chemical substances by chemical adsorption, physicaladsorption, specific reaction with bonding substances provided fixed tothe carrier, and other ways. Moreover, the carrier may be formed from aporous member, a corrugated surface member, or a fibrous member so as toincrease the reaction ability and the bondability with the chemicalsubstances.

The carrier is preferably held by self-weight, frictional force, orremote force to a degree which keeps the carrier from floating up orbeing moved by the presence of fluid in the carrier housing section, orby the drawing/discharging of fluid into/out of the carrier housingsection, so that the fluid can contact sufficiently with the carrieraccording to the amount of the fluid. Particularly in the case where theligand or the like is fixed to the carrier in a position according itschemical structure in order to measure the luminescence, the position ofthe carrier is preferably unchanged.

According to this aspect of the invention, regarding a carrier which isfixed or able to be fixed with various substances, the arrangement issuch as to enable processes to be performed while accommodated in thecarrier housing section. Therefore, the attraction control or thedrawing control for accommodating and holding the carrier in the housingsection become unnecessary, so that the complicated reaction processesare simplified, and the processes can be easily performed with a smallscale apparatus structure.

Moreover, according to this aspect of the invention, regarding a carrierwhich is fixed or able to be fixed with various substances, thearrangement is to accommodate and remove these substances by a routewhich is different from a route for drawing/discharging a fluid orsubstances suspended in the fluid. Therefore, the process for separatingthe fluid and the carrier becomes unnecessary, so that the complicatedreaction processes are simplified and the processes can be easilyperformed with a small scale apparatus structure.

Furthermore, according to this aspect of the invention, regarding acarrier which is fixed or able to be fixed with various substances, thearrangement is such as to enable easy removal of the substances from thecarrier housing section accommodating them. Therefore, it becomespossible to easily exchange and preserve the carrier or perform otherprocesses with respect to the carrier, so that the efficiency, thereliability and the certainty of processes can be increased.

Moreover, according to this aspect of the invention, only bydrawing/discharging a fluid while holding the carrier in the carrierhousing section and transferring the carrier housing section, variousprocesses, for example, reacting, washing, temperature control,separating, mixing, pipefiting, clarifying, isolating, eluting, andextracting can be performed, so that the processes can be effectively,rapidly and easily performed.

A second aspect of the invention is a carrier housing/processingapparatus wherein the carrier housing section has a large diametersection which accommodates the carrier and a small diameter sectionwhich has the inlet/outlet at the tip and has a smaller diameterenabling insertion into containers provided outside.

Furthermore, the arrangement may be such that the carrier housingsection has a large diameter section, a small diameter section which hasa smaller diameter than the large diameter section, and an intermediatediameter section which is provided between the large diameter sectionand the small diameter section having a diameter intermediate betweenthem. In this case, the arrangement is such that the intermediatediameter section accommodates the carrier. In this case, the arrangementis such that, by forming the intermediate diameter section into a sizecapable of accommodating the carrier but making the volume of the restof the space in the intermediate diameter section in the case ofaccommodating the carrier sufficiently smaller than the volume of thecarrier, the processes can be performed on a fluid which has asufficiently smaller volume of the fluid being drawn than the volume ofthe carrier. Moreover, by setting the volume of the large diametersection to the maximum volume of the container which accommodates theliquid being the object of the process, it becomes possible to also copewith a process which manages liquid of the maximum volume capable ofbeing accommodated in the container. The boundary of the small diametersection, the intermediate diameter section, and the large diametersection may be formed so as not to rapidly change in diameter, but togradually change from the large diameter to the small diameter.

According to this aspect of the invention, by providing the smalldiameter section which is capable of insertion into external containers,the housing apparatus may be transferred between containers includingcontainers set in a constant temperature, while accommodating thecarrier to draw/discharge liquids such as various reagents, suspensions,and the like accommodated in the respective containers, so thatreacting, washing, temperature control, separating, mixing, pipefitting,clarifying, isolating, eluting, and extracting can be performed.Therefore, a series of processes may be converted to the transferringprocess between containers so as to simplify the control.

A third aspect of the invention is a carrier housing/processingapparatus wherein the carrier housing section has an opening having asize enabling the carrier to pass through, and the drawing/dischargingsection is provided with a nozzle which detachably connects with theopening, and the carrier is formed in a size capable of passing throughthe opening but not capable of passing through the inlet/outlet.

Here, the carrier may be previously accommodated in the housing sectionprior to installation onto the nozzle. In this case, the opening may bedetachably covered by a lid body so as to enclose the carrier.

According to this aspect of the invention, since the carrier isaccommodated into the carrier housing section so as to be able to betaken out, then by exchanging the carrier, it becomes possible toreliably prevent cross-contamination, and to preserve the carrier, andto perform further processes.

A fourth aspect of the invention is a carrier housing/processingapparatus wherein the carrier is; a particle having a larger diameterthan the inlet/outlet, a block member having a shape not capable ofpassing through the inlet/outlet, a sheet member, a wire like memberformed by bending in a predetermined size, or an indeterminate member.Here, block-like member includes spherical, cylindrical, and prismaticmembers.

According to this aspect of the invention, various materials can be usedso as to diversify the processes.

A fifth aspect of the invention is a carrier housing/processingapparatus wherein the plurality of carriers are a plurality of kinds.

According to the this aspect of the invention, by accommodating aplurality of carriers, a plurality of processes may be performed inparallel so as to perform the processes effectively, rapidly and easily.

A sixth aspect of the invention is a carrier housing/processingapparatus wherein the carrier is provided with an adhesion preventionsection such as a projection, a ditch, a corrugated surface, for keepingthe carrier from being adhered to the inner wall of the carrier housingsection.

According to this aspect of the invention, by providing the adhesionprevention section such as a projection, a ditch, a corrugated surfacefor keeping the carrier from being adhered to the inner wall of thecarrier housing section, the contact efficiency of the carrier and afluid can be increased.

A seventh aspect of the invention is a carrier housing/processingapparatus wherein the carrier housing section is provided with anadhesion prevention section such as a projection, a ditch, a corrugatedsurface, for keeping from being adhered to the carrier.

According to this aspect of the invention, by providing the adhesionprevention section such as a projection, a ditch, a corrugated surfacefor keeping the carrier from being adhered with the inner wall of thecarrier housing section, the contact efficiency of the carrier and afluid can be increased.

An eighth aspect of the invention is a carrier housing/processingapparatus wherein the carrier is; a member having through holes, apermeable membrane member, a porous member, or a mesh member, which isheld at a predetermined position in the carrier housing section so as todivide and partition the carrier housing section into upper and lowerspaces, and allow a fluid to pass therethrough.

According to this aspect of the invention, since the carrier is providedso that the housing section is divided and separated into upper andlower spaces, and a fluid can pass through, the contact efficiency withthe fluid is high.

A ninth aspect of the invention is a carrier housing/processingapparatus wherein the carrier is held at the bottom of the carrierhousing section, which is a predetermined position, by self-weight, andcarrier holding sections such as projections, ditches, corrugatedsurfaces are provided at the bottom so as to keep the carrier fromblocking passage of the fluid.

According to this aspect of the invention, since carrier holdingsections are provided at the bottom so as not to block passage of afluid, the carrier and the fluid can be reliably contacted to increasethe efficiency of the process.

A tenth aspect of the invention is a carrier housing/processingapparatus wherein the carrier housing section is formed from atranslucent member, and a measuring apparatus which measuresluminescence on the carrier is provided outside of the carrier housingsection.

According to this aspect of the invention, since the measuring apparatuswhich measures the luminescence is provided, not only reaction but alsoprocesses including measuring may be consistently performed.

An eleventh aspect of the invention is a carrier housing/processingapparatus wherein in the carrier housing section, a side face providedwith the measuring equipment is formed in a plane. Accordingly, theluminescence may be reliably measured.

According to this aspect of the invention, the measurement of theluminescence may be reliably performed.

A twelfth aspect of the invention is a carrier housing/processingapparatus wherein the carrier contains a magnetic substance and thecarrier is held in a predetermined position of the carrier housingsection due to a magnetic field exerted from outside of the carrierhousing section.

According to this aspect of the invention, by holding the carrier in apredetermined position of the housing section due to the magneticsubstance, the luminescence including position may be reliably measured.

A thirteenth aspect of the invention is a carrier housing/processingapparatus wherein the carrier is a glass or its surface is coated with aglass.

According to this aspect of the invention, by using a carrier coatedwith a glass on the surface, DNA substances can be easily captured.

A fourteenth aspect of the invention is a carrier housing/processingmethod comprising; a drawing/contacting step for, with respect to ahousing section which accommodates one or a plurality of carriers fixedor able to be fixed with chemical substances such as ligands and has aninlet/outlet which enables a fluid to pass through but does not enablethe carriers to pass through, drawing fluid through the inlet/outletfrom external containers by a drawing/discharging section, to contactthe carriers which are held in the carrier housing section byself-weight of the carrier, frictional force with the inner wall of thecarrier housing section, or remote force from outside with respect tothe carrier, with the drawn fluid; and a discharging step fordischarging only the fluid through the inlet/outlet by thedrawing/discharging section, in a state where the carrier isaccommodated in the carrier housing section.

This aspect of the invention has a similar effect to the effectdescribed in the first aspect of the invention.

A fifteenth aspect of the invention is a carrier housing/processingmethod further comprising a transferring step for transferring theinlet/outlet relatively with respect to containers provided outside.

According to this aspect of the invention, various processes may beperformed by transferring the inlet/outlet between containers.

A sixteenth aspect of the invention is a carrier housing/processingmethod wherein the reaction step has a step for repeatedly drawing anddischarging a fluid with respect to the carrier housing section.

According this aspect of the invention, by repeatedly drawing anddischarging a fluid with respect to the carrier housing section, thereaction can be performed effectvely and reliably.

A seventeenth aspect of the invention is a carrier housing/processingmethod further comprising an accommodating step for accommodating thecarrier in the carrier housing section from an opening having a sizeenabling the carrier to pass through.

According to this aspect of the invention, since the carrier isaccommodated in the carrier housing section so as to be able to be takenout, then by exchanging the carrier or the like, it becomes possible toreliably prevent cross-contamination, and to preserve the carrier, andto perform further processes.

An eighteenth aspect of the invention is a carrier housing/processingmethod further comprising a removing step for removing the carrier fromthe carrier housing section through an opening having a size enablingthe carrier provided in the carrier housing section to pass through.

According to this aspect of the invention, since the carrier isaccommodated in the carrier housing section so as to be able to be takenout, then by exchanging the carrier or the like, it becomes possible toreliably prevent cross-contamination, to preserve the carrier, and toperform further processes.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a carrier housing reactoraccording to the first embodiment of the present invention.

FIG. 2 is a schematic illustration of carrier housing reactors ofaccording to the second and the third embodiments of the presentinvention.

FIG. 3 is a perspective illustration of a carrier housing reactor ofaccording to the forth embodiment of the present invention.

FIG. 4 shows an example of a process using the carrier housing reactoraccording to the first embodiment of the present invention.

BEST MODE FOR CARRYING OUT THE INVENTION

Next is a description of, a carrier housing/processing apparatus 10according to a first embodiment of the present invention, based onFIG. 1. The description of the respective embodiments should not beconsidered as limiting the present invention, unless particularlyspecified.

As shown in FIG. 1(a), the carrier housing/processing apparatus 10according to the present embodiment has one spherical carrier 11 capablefixing DNA having a predetermined base sequence as a ligand on thesurface, and a fluid inlet/outlet 12 for, and is provided with anapproximate cylindrical carrier housing section 13 accommodating thespherical carrier 11, a drawing/discharging section 14 which draws anddischarges a fluid with respect to the carrier housing section 13through the inlet/outlet 12, and a transferring section (not shown)which relatively transfers the fluid inlet/outlet 12 of the carrierhousing section 13, with respect to containers 15 to 18 externallyprovided.

Moreover, the carrier housing section 13 has a large diameter section 19which accommodates the spherical carrier 11, and a small diametersection 20 which has the inlet/outlet 12 at the tip and has a smallerdiameter than the large diameter section, enabling insertion into thecontainers 15 to 18. The diameter of the spherical carrier 11 is formedlarger than the internal diameter of the small diameter section 20, thatis the bore of the inlet/outlet 12, so as to keep the spherical carrier11 from passing through the small diameter section 20 and beingdischarged out of the carrier housing section 13. Furthermore, thecarrier housing section 13 has an opening 21 having a size enabling thespherical carrier 11 to pass through.

The drawing/discharging section 14 has; a nozzle section 22 whichdetachably connects with the opening 21 at the tip, a cylinder 23, and athin pipe 24 which connects the cylinder 23 and the nozzle section 22.Furthermore, an O-ring 25 for maintaining watertightness, is providedbetween the nozzle section 22 and the carrier housing section 13.

At the bottom of the large diameter section 19 in the carrier housingsection 13, there are provided carrier holding sections 26 protrudingupwards so as to hold the spherical carrier 11. The carrier holdingsections 26 are provided arranged for example at three or four places atequal intervals around the circumference of the hole in the center ofthe bottom of the large diameter section 19.

The containers 15 to 18 accommodate specimens, reagents and the likerequired according to the sequence of the processes. The container 17 isaccommodated in a thermostatic block 27 which keeps a predeterminedtemperature so as to maintain a liquid accommodated in the container 17at the predetermined temperature.

To the spherical carrier 11 is fixed or able to be fixed, apredetermined ligand, for example, a single strand DNA. The sphericalcarrier 11 itself is formed in a porous shape, increasing the holdingability of the ligand and enabling a liquid to pass through inside so asto increase the possibility that the ligand and the liquid encounter.The spherical carrier 11 is formed so as to have a density sufficientlylarger than the density of a liquid drawn and discharged with respect tothe carrier housing section 13, and is mounted on the carrier holdingsections 26 being the protruding members, by self-weight.

The spherical carrier 11 may be formed from for example, a resin, aglass, a ceramic, a metal, and the like, including nylon, polyethylene,polyester, polypropylene, urethane, gum, and the like. Moreover, thematerials may be combined so as to have the self-weight, by placing aweight formed from a metal inside, and forming the exterior from aresin.

FIG. 1(b) shows a carrier housing/processing apparatus according toanother embodiment.

The apparatus differs from the carrier housing/processing apparatus 10according to the first embodiment, in that a sheet carrier 31 isprovided instead of the spherical carrier 11 inside a carrier housingsection. The dimensions of at least two of the width, the length, andthe thickness of the sheet carrier 31 are formed larger than theinternal diameter of the small diameter section 20, that is the bore ofthe inlet/outlet 12, so as to keep the sheet carrier 31 from passingthrough the small diameter section 20 and being discharged out of thecarrier housing section 30.

Moreover, the carrier housing section 30 has an opening 21 having a sizeenabling the sheet carrier 31 to pass through. Due to the shape of thesheet carrier 31, the sheet carrier 31 does not dog in the passage ofthe small diameter section 20 leading to the inlet/outlet. Therefore,the carrier holding section 26 is not provided. The material of thesheet carrier 31 is similar to the case of the abovementioned sphericalcarrier 11.

FIG. 2(a) and (c) show an example of a carrier housing section 32according to a second embodiment.

The carrier housing section 32 is approximate cylindrical havingapproximate three steps accommodating the spherical carrier 11 inside.The carrier housing section 32 has a fluid inlet/outlet 36, and isfitted to a nozzle section 38 of a drawing/discharging section whichdraws and discharges a fluid with respect to the carrier housing section32, passing through the inlet/outlet 36. Moreover it is possible totransfer the inlet/outlet 36 of the carrier housing section 32relatively with respect to a container (not shown) provided outside, bya transferring section (not shown).

The carrier housing section 30 has a large diameter section 33 which isable to accommodate a fluid, with its opening 40 fitted to the nozzlesection 38 via an O-ring 39, a small diameter section 35 which has theinlet/outlet 36 at the tip and has a smaller diameter than the largediameter section enabling insertion into the containers, and anintermediate diameter section 34 which is provided between the largediameter section 33 and the small diameter section 35, having a diameterintermediate between them, and which accommodates the spherical carrier11.

Moreover, the diameter of the opening 40 of the large diameter section33 is formed larger than the spherical carrier 11, enabling thespherical carrier 11 to pass through. According to the presentembodiment, the reaction process may be performed with the degree of thevolume of the rest of the space in the intermediate diameter section 34accommodating the spherical carrier 11, that is the small amount offluid having a sufficiently smaller volume than the volume of thespherical carrier 11. At the bottom of the intermediate diameter section34, as shown in FIG. 2 (c), there are provided carrier holding sections37, protruding upwards at a plurality of places so as to hold thespherical carrier 11.

FIG. 2(b) and (d) show an example of a carrier housing section 41according to the third embodiment.

The carrier housing section 41 is approximate cylindrical havingsubstantially two steps accommodating two spherical carriers 11 a and 11b. The carrier housing section 41 has a fluid inlet/outlet 44 and isfitted to a nozzle section 47 of a drawing/discharging section whichdraws and discharges a fluid with respect to the carrier housing section41, passing through the inlet/outlet 41. Moreover it is possible totransfer the inlet/outlet 44 of the carrier housing section 41relatively with respect to a container (not shown) provided outside, bya transferring section (not shown).

The carrier housing section 41 has a large diameter section 42 which isable to accommodate a fluid, with its opening 48 fitted to the nozzlesection 47 via an O-ring 46, and a small diameter section 43 which hasthe inlet/outlet 44 at the tip and has a smaller diameter than the largediameter section enabling insertion into the containers. Moreover, inthe large diameter section 42, a filter 45 enabling only air to passthrough, is provided so as to divide the large diameter section into twoupper and lower spaces. Accordingly, a liquid drawn into the lower spacecan be kept from invading into the upper space, so as to reliablyprevent cross-contamination due to contamination of the nozzle section47 itself.

Moreover, at the bottom of the large diameter section 42, approximatetriangular carrier holding sections 49 which hold the spherical carrier11 a without blocking the flow of fluid, are radially provided rising upfrom the vicinity of the center along the radial direction.

FIG. 3 shows a carrier housing section 50 according to a fourthembodiment.

The carrier housing section 50 has an attachment section 52 which isable to accommodate a fluid, with its opening 55 fitted to thecylindrical nozzle section (not shown) via an O-ring a measurementhousing section 51 which communicates with the attachment section 52,formed from an approximate prismatic transparent or semitransparentmember capable of accommodating a sheet carrier 31 inside, anintermediate section 54 which is approximate pyramidal and communicateswith the measurement housing section 51, and a small diameter section 53which is provided on the intermediate section 54, formed thinner thanthe large diameter section enabling insertion into containers providedoutside, and having a fluid inlet/outlet 56 at the tip. Moreover, it ispossible to transfer the inlet/outlet 56, that is the carrier housingsection 50 relatively with respect to containers provided outside, by atransferring section.

The intermediate section 54 plays a role of a carrier holding sectionwhich holds the aforementioned sheet carrier 31. On the side face of themeasurement housing section 51 is provided a luminescent section or aphotoreceptive section of a photometer, enabling measurement of theluminescence from the sheet carrier 31 accommodated in the measurementhousing section 51, which transmitting orthogonally to the side face.Accordingly, the measurement can be performed more certainly andreliably.

FIG. 4 illustrates a case where a process is performed in which DNA isextracted from cells using a carrier housing/processing apparatus havingcarrier housing sections 13 and 32 accommodating various carriers 11,31, 57, 58, 59, and 60.

FIG. 4(a) shows a case where the spherical carrier 11 is accommodated inthe carrier housing section 13 as described above. FIG. 4(b) shows acase where a ribbon carrier 57 is accommodated in the carrier housingsection 32. The ribbon carrier 57 is a wire like member which is notdeformed unless a certain degree of force is applied, and is bent in ashape so as not to pass through the small diameter section 20, that isthe inlet/outlet 12, and is held in the carrier housing section 32 byself-weight.

FIG. 4(c) shows a case where the sheet carrier 31 is accommodated in thecarrier housing section 30. The sheet carrier 31 is the same asdescribed in FIG. 1.

On the other hand, FIG. 4(d) shows a case where a cylindrical carrier 58is accommodated in the carrier housing section 13. The diameter of thecylindrical carrier 58 is formed larger than the internal diameter ofthe small diameter section 20, that is the bore of the inlet/outlet 12,so as to keep the cylindrical carrier 58 from passing through the smalldiameter section 20 and being discharged out of the carrier housingsection 13. The cylindrical carrier 58 is held in the carrier housingsection 30 by self-weight, or by frictional force with the inner wall ofthe carrier housing section 13. The material of the cylindrical carrier58 is similar to the material described for the spherical carrier 11.

FIG. 4(e) shows a case where the porous carrier 59 is accommodated inthe carrier housing section 13. The porous carrier 59 is formed from aporous material and provided with a large number of through holesenabling a liquid to pass through inside. Here, an example is shownwhere the porous carrier 59 is cylindrical. The diameter is formedlarger than the internal diameter of the small diameter section 20, thatis the bore of the inlet/outlet 12. Accordingly, the surface area isincreased so that the capturing ability for bonding a target substancecan be increased.

Furthermore, FIG. 4(f) shows a case where an indeterminate carrier 60 isaccommodated in the carrier housing section 13. In this case, thediameter of the indeterminate carrier 60 has a shape or a size which isunable to pass through the small diameter section 20, that is theinlet/outlet 12, so as to keep the indeterminate carrier 60 from passingthrough the small diameter section 20 and being discharged out of thecarrier housing section 13. The indeterminate carrier 60 is held in thecarrier housing section 30 by self-weight, or by frictional force withthe inner wall of the carrier housing section 13.

The case of FIG. 4(a) is described.

In step S1, for example, in order to destruct cells such as microbialbodies, a cell lysate solubilized with high concentration guanidineisothiocyanate (protein denaturant) or surfactant, to bare DNA closed ineach cell, is accommodated in a container 15.

Moreover, in order to capture the DNA in the lysate, the sphericalcarrier 11 coated with a material capable of bonding the DNA, forexample a glass or a silica gel, is inserted into the carrier housingsection 13 from the opening 21 and accommodated therein.

In step S2, the small diameter section 20 of the carrier housing section13 is relatively transferred to the container 15 accommodating the celllysate in which the cells were lysed, and is inserted into the container15. Then, the lysate in the container 15 is drawn into the carrierhousing section 13 accommodating the spherical carrier 11, by thedrawing/discharging section 14 until the spherical carrier 11 iscompletely immersed in the lysate, and is then discharged. This actionis repeated several times. As a result, the spherical carrier 11accommodated in the carrier housing section 13 and the lysate contactwith each other so that the DNA in the lysate is absorbed into thespherical carrier 11. Since it is under the presence of thiocyanate ions(also called chaotropic ions or chaotrope ions) which play a role todehydrate the hydrated water in the lysate, DNA is in the state of beingabsorbed easily into the silica surface. The reason why it is in thestate of being absorbed easily, is generally that since the absorptionability of silica gel decreases according to the amount of hydratedwater, the absorption ability increases by capturing the hydrated water.

In step S3, the residual liquid of the lysate is discharged from thecarrier housing section 13 into the container 15. Then in a state withthe lysate discharged from the carrier housing section 13 and the DNAseparated by the spherical carrier 11, the carrier housing section 13 istransferred relatively with respect to a region where various containersare mounted, to a container 16 accommodating a washing reagent. In thisseparation state, proteins as well as the DNA are not completelyremoved, and are in the absorbed state.

In step S4, the small diameter section 20 is inserted into the container16, and a protein denaturant having a similar function as in step Si,and an ethanol which are washing reagents, are used so as to performwashing which removes the proteins without removing the DNA from thespherical carrier 11. That is, the proteins are denatured by the proteindenaturant so as to destroy the proteins, and hydration with DNA isprevented by the ethanol so as to generate precipitation. In this case,since the ethanol is 70% concentration, components having the functionof generating precipitation and contained as the absorption liquid andthe washing solution are desalinized, and the solutions are replaced bysolutions of low salt concentration. As a result, the hydration with theDNA is prevented at the same time.

In step S5, in a state with the spherical carrier 11 absorbing thewashed DNA accommodated therein, the carrier housing section 13 isfurther transferred relatively with respect to the region where variouscontainers are mounted, to a container 18 accommodating an eluation. Thesmall diameter section 20 is then inserted into the container 18, andthe drawing and the discharging are repeated so as to elute the DNAcaptured by the spherical carrier 11 into the eluation. Here, theeluation is performed, for example using miliQ or TE (Tris-EDTA) buffersolution. Then, the DNA dehydrated in step S4 is re-hydrated anddissolved. At the same time, the silica surface becomes a state wherethere is no chaotrope ions and is easier to be hydrated. Sinceoriginally the interaction between the DNA and the silica is more than alittle, it is more effective if the eluton is performed while increasingthe temperature, or mixing.

In step S6, all of the liquid in the carrier housing section 13 isdischarged into the container 18 so as to obtain the DNA.

Instead of following the elution processes of step S5 and step S6, theDNA may be taken out from the carrier housing section 13 while bondedwith the spherical carrier 11, to use for other processes and the like.

The above described respective embodiments have been described in detailin order to better understand the present invention, and in no way limitother aspects. Consequently, the embodiments can be modified within ascope which does not alter the gist of the invention. For example, inthe embodiments, only the case of the spherical carrier 11 was describedin detail. However the present invention is not limited to this case andis also applicable to the ribbon carrier 57 such as a wire like member,the sheet carrier 31, the cylindrical carrier 58, the porous carrier 59,and the indeterminate carrier 60.

Furthermore, in the present invention, even if the member is a flexibleslender member such as ribbon or string which is fixed or able to befixed with chemical substances such as one or more kinds of ligands onthe side face thereof, as long as it is an integrated slender memberwhich is coiled using or not using a supporting body such as acylindrical core or the like, and integrated by lamination or alignment,and is formed in a size or a shape which is unable to pass through theinlet/outlet, and which allows drawing and discharging of a fluid whilebeing held in the carrier housing section, it may be used as thecarrier.

In the case of a flexible slender member or a wire like member, byfixing or being able to be fixed with the chemical substances includingliving bodies along the circumference direction orthogonal to thelongitudinal direction, the chemical substances can be accurately andeasily arranged in the same manner on a side face viewed from anydirection. Therefore, a reaction or a measurement process may beperformed on the side face viewed from any direction. Furthermore, bylowering the density of chemical substances including ligands withrespect to all side faces of the slender member, manufacture can beeasier and reliability can be increased. On the other hand, at the timeof processing, by accommodating the integrated slender member,processing efficiency can be increased. Moreover, at the time ofmeasuring, since the arrangement of chemical substances can be reliablycorresponded along a one-dimensional path, measurement reliability ishigh. The flexible slender member includes for example a member formedfrom a chemical fiber such as nylon or the like.

The carrier includes a member having one or more kinds of chemicalcompounds arranged at intervals, so that their positions can bespecified, and a member having one or more kinds of chemical compoundsnot arranged so that their positions can be specified, but fixed or ableto be fixed.

Moreover, the abovementoned respective components, the respectivecarriers, the respective carrier housing sections, the carrier holdingsections, the containers, the drawing/discharging sections, the smalldiameter sections, the large diameter sections, the intermediatediameter section, the intermediate section, the nozzle sections, and thelike, or the respective apparatus may be arbitrarily combined withappropriate modification.

Furthermore, in the abovementioned examples, only the case of DNAextraction was described. However the carrier may be fixed with ligandsor the like in order to detect a target substance. Moreover, the ligandis not limited to DNA but includes genetic substances such asoligonucleotides and RNA, immunity substances, proteins, sugar chains,and further includes pheromones, allomones, mitochondorias, virus,plasmids, and the like.

Moreover, the abovementioned reagents or substances show one example,and other reagents or substances may be used. Furthermore, a carriercapturing DNA or the like may be taken out from the carrier housingsection and preserved, or made an object of other processes.

1. A carrier housing/processing apparatus comprising; one or a pluralityof carriers fixed or able to be fixed with chemical substances such asligands; a carrier housing section which is provided with a fluidinlet/outlet and which accommodates said carrier; a drawing/dischargingsection which draws and discharge a fluid through said inlet/outlet withrespect to said carrier housing section; and a transferring sectionwhich transfers said inlet/outlet relatively with respect to containersprovided outside, wherein said carrier is formed in a size or a shapenot allowing said carrier to pass through said inlet/outlet, and in astate of holding said carrier in said housing section, by self-weight ofsaid carrier, frictional force between said carrier and the inner wallof said housing section, or remote force from outside with respect tosaid carrier, a fluid is drawn and discharged.
 2. A carrierhousing/processing apparatus according to claim 1, wherein said carrierhousing section has a large diameter section which accommodates saidcarrier and a small diameter section which has said inlet/outlet at thetip and has a smaller diameter enabling insertion into containersprovided outside.
 3. A carrier housing/processing apparatus according toclaim 1, wherein said carrier housing section has an opening having asize enabling said carrier to pass through, and said drawing/dischargingsection is provided with a nozzle which detachably connects with saidopening, and said carrier is formed in a size capable of passing throughsaid opening but not capable of passing through said inlet/outlet.
 4. Acarrier housing/processing apparatus according to either one of claim 1and claim 3, wherein said carrier is; a particle having a largerdiameter than said inlet/outlet, a block member having a shape notcapable of passing through said inlet/outlet, a sheet member, a wirelike member formed by bending in a predetermined size, or anindeterminate member.
 5. A carrier housing/processing apparatusaccording to any one of claim 1 through claim 4, wherein said pluralityof carriers are a plurality of kinds.
 6. A carrier housing/processingapparatus according to any one of claim 1 through claim 5, wherein saidcarrier is provided with an adhesion prevention section such as aprojection, a ditch, a corrugated surface, for keeping said carrier frombeing adhered to the inner wall of said carrier housing section.
 7. Acarrier housing/processing apparatus according to any one of claim 1through claim 6, wherein said carrier housing section is provided withan adhesion prevention section such as a projection, a ditch, acorrugated surface, for keeping from being adhered to said carrier. 8.An carrier housing/processing apparatus according to any one of claim 1through claim 7, wherein said carrier is; a member having through holes,a permeable membrane member, a porous member, or a mesh member, which isheld at a predetermined position in said carrier housing section so asto divide and partition said carrier housing section into upper andlower spaces, and allow a fluid to pass therethrough.
 9. A carrierhousing/processing apparatus according to any one of claim 1 throughclaim 8, wherein said carrier is held at the bottom of said carrierhousing section, which is a predetermined position, by self-weight, andcarrier holding sections such as projections, ditches, corrugatedsurfaces are provided at the bottom so as to keep said carrier fromblocking passage of said fluid.
 10. A carrier housing/processingapparatus according to any one of claim 1 through claim 9, wherein saidcarrier housing section is formed from a translucent member, and ameasuring apparatus which measures luminescence on said carrier isprovided outside of said carrier housing section.
 11. A carrierhousing/processing apparatus according to claim 10, wherein in saidcarrier housing section, a side face provided with said measuringequipment is formed in a plane.
 12. A carrier housing/processingapparatus according to any one of claim 1 through claim 11, wherein saidcarrier contains a magnetic substance and said carrier is held in apredetermined position of said carrier housing section due to a magneticfield exerted from outside of said carrier housing section.
 13. Acarrier housing/processing apparatus according to any one of claim 1through claim 12, wherein said carrier is a glass or its surface iscoated with-a glass.
 14. A carrier housing/processing method comprising;a drawing/contacting step for, with respect to a housing section whichaccommodates one or a plurality of carriers fixed or able to be fixedwith chemical substances such as ligands and has an inlet/outlet whichenables a fluid to pass through but does not enable said carriers topass through, drawing fluid through said inlet/outlet from externalcontainers by a drawing/discharging section, to contact said carrierswhich are held in said carrier housing section by self-weight of saidcarrier, frictional force with the inner wall of said carrier housingsection, or remote force from outside with respect to said carrier, withthe drawn fluid; and a discharging step for discharging only said fluidthrough said inlet/outlet by said drawing/discharging section, in astate where said carrier is accommodated in said carrier housingsection.
 15. A carrier housing/processing method according to claim 14,further comprising a transferring step for transferring saidinlet/outlet relatively with respect to containers provided outside. 16.A carrier housing/processing method according to either one of claim 14and claim 15, wherein said reaction step has a step for repeatedlydrawing and discharging a fluid with respect to said carrier housingsection.
 17. A carrier housing/processing method according to any one ofclaim 14 through claim 16, further comprising an accommodating step foraccommodating said carrier in said carrier housing section from anopening having a size enabling said carrier to pass through.
 18. Acarrier housing/processing method according to any one of claim 14through claim 17, further comprising a removing step for removing saidcarrier from said carrier housing section through an opening having asize enabling said carrier provided in said carrier housing section topass through.